Proteoglycans (PGs) are largely responsible for the special mechanical properties of articular cartilage, such as its stiffness in compression. Osteoarthritis, which is principally a disease of the elderly, is marked by the loss of PGs from articular cartilage. It is the purpose of the proposed studies to obtain new and fundamental information concerning the macromolecular organization of PGs (a) in articular cartilages of normal individuals of varying ages and (b) in osteoarthritis. PGs will be extracted from histochemically graded cartilage samples with either a dissociating solvent (4M guanidine) or with neutral salt. Tissue residues will then be extracted after digestion with collagenase, to liberate those PGs more intimately associated with collagen. PGs in the various extracts will be characterized chemically, physicochemically and immunologically. Particular attention will be paid to the presence of uniquely small PGs, previously identified by the applicant in articular cartilages; the tissue content of the small PG will be determined in various samples of normal and diseased cartilage. In organ culture of cartilage slices metabolic relationships between larger and smaller PGs will be examined in the hope of defining a precursor-product relationship. Animal models of experimental osteoarthritis will be used, and changes in PGs examined from the very earliest stages of the disease onward. It is intended to study in systematic fashion the composition and organization of PGs of articular cartilage in order to determine whether changes occur in aging and to compare "normal" cartilage from aged individuals with osteoarthritic cartilage. The ultimate aim is to obtain insight into the basic abnormality of cartilage matrix in osteoarthritis, the most common articular disease of man.